Pregnancy/Lactation

Interactions

Adverse Reactions

Allergic reactions and contact dermatitis have been reported. Anaphylaxis has resulted from the use of intravenous (IV) preparations in which the vehicle is a castor oil derivative.

Toxicology

Deaths from castor plant/bean ingestion are rare. Ricin, a toxic protein of the castor bean, has been used as a biological weapon.

Botany

Castor, a common annual ornamental native to the West Indies, grows to heights of 12 m and bears broad, deeply-lobed leaves on broad stalks. The flowers develop into spiny capsules, each containing 3 seeds. As the capsules dry, they explode, scattering the glossy, speckled oval beans. 1 , 2 , 3 The castor plant has been naturalized to temperate regions of the continental United States and Hawaii. 4 , 5

History

The name Ricinus is derived from the Latin word for insect because the seeds resemble beetles in shape and markings. Castor beans are used as art objects and ornaments. The Egyptians used castor oil as a lamp oil and an unguent, also ingesting the oil with beer as a purgative. The roots, leaves, and seeds have a place in traditional folk remedies throughout the world. Other recorded medicinal uses include induction of labor, as a cathartic, as a contraceptive cream, and as a skin emollient. 2 , 3 , 4 , 5 , 6 , 7 The fast-drying, nonyellowing oil has been used in the manufacture of high-grade lubricants for industrial machinery and aircraft engines and in dyes, inks, paint, and varnishes. 2 , 3 , 6 The castor cake or pulpy residue that remains after oil extraction has been used as animal feed and as fertilizer despite its unsuitability due to traces of toxins. 2

Ricin was developed as a biological warfare agent in the 1920s and was considered for use during World Wars I and II. Arrests for terrorism activity have been made since the 1990s for the possession of ricin or castor beans. 3 , 4 , 5

Initially hailed as a potential antitumor agent, ricin underwent phase 1 and 2 clinical trials for tumor-specific antibody action. However, the dose-limiting adverse reactions hypo-albuminema and edema, as well as the lack of specificity and intrinsic immunogenicity precluded approval. 4

Chemistry

Cold expression of the kernels yields about 33% medicinal quality castor oil. 8 The pulpy residue left after expression of the oil is known as the castor pomace. 9 An additional 13% to 20% of lesser quality fixed oil can be obtained by further extraction. 8 , 9 Castor oil is a mixture of triglycerides, of which 75% to 90% is ricinoleic acid. 2 , 10 Lesser amounts (1% to 4%) of linoleic, oleic, palmitic, and stearic acids are also found. 2 Further refinement by steam, filtration, and bleaching removes some of the toxins (such as ricin and ricinine) and the allergen CB-1A. 3 , 8

Ricin, a 65 Kda glycoprotein phytotoxin, consists of a neutral A chain and an acidic B chain connected by disulfide bonds. The A chain inhibits protein synthesis (causing cell death), while the B chain serves as a carrier that binds the protein to cell surfaces and facilitates internalization, similar to other type II ribosome inactivating proteins such as the bacterial toxins from diphtheria, cholera, and anthrax. 3

Ricin can be separated into the highly toxic ricin D, acidic ricin, and basic ricin. The alkaloid ricinine found in the seeds is also present in the leaves. 3 , 4

Uses and Pharmacology

Chemical warfare

Ricin has been developed as a biological warfare agent. 3 , 4 , 5 The immunogenicity that precluded the use of ricin as an antitumor agent is now being used in the development of an antiricin vaccine as a defensive biological agent. Animal studies have investigated active immunization and passive prophylaxis with limited success. A genetically engineered form of a ricin subunit elicited antibodies in animals and may protect against larger doses of ricin. 3 , 4 , 5

Induction of labor

Castor oil was widely used to induce labor by US midwives in the past, but use has now declined. 11 , 12 Reviews of trials and case reports find no evidence supporting this use. 12 , 13 Doses cited range from 5 to 120 mL; however, no data are available to support these doses. 11 One proposed mechanism of action is stimulation of endogenous prostaglandin E synthesis by ricinoleic acid. 11

No morbidity or mortality data are available in these studies for either mother or newborn. Nausea was commonly reported. Complications included amniotic fluid embolism after a single 30 mL dose and uterine rupture after a 5 mL dose in a woman with a previous cesarean delivery. 11

Laxative/purgative

The oil has long been used as a laxative and purgative following treatment for intestinal parasites. The components of castor oil are known to exert a cathartic effect. 6 , 8 , 14

Other usesOphthalmic

A small randomized clinical trial evaluating the efficacy of castor oil eye drops in treating meibomian gland dysfunction resulted in an increase in tear stability and a lubricating effect. 15

Vehicle/solubilizer

Castor oil is used for its water-insoluble lipid and surfactant properties in certain oral and injectable drugs and vitamin preparations, including cyclosporin A, phytonadione, tacrolimus, and carbemazepine. 16 , 17 , 18

Wound management

Castor oil is found in topical wound care preparations, often combined with Peru balsam and trypsin. 19 , 20

Dosage

Dosages of castor seed oil vary considerably, with 5 to 120 mL reported as a single dose in the literature. The lower dose has been used as a purgative, and the higher dose has been used to induce labor. 3 , 4

Pregnancy/Lactation

Interactions

The kinetics of digoxin were affected by coadministration of the castor oil derivative polyoxyl 35 castor oil. Oral cremophor delayed and enhanced absorption of an oral dose of digoxin 0.5 mg in healthy adults. The increase in plasma digoxin concentrations did not result in clinical effects. 17 Experimental interactions with IV doxorubicin and doxorubicinol and oral saquinavir also have been observed, with proposed action via interference with the efflux pump P-glycoprotein membrane transporter. Interactions with other drugs with relatively low bioavailability, such as amiodarone and phenytoin, are theoretically possible. 17

Adverse Reactions

Immunoglobulin E-mediated allergy to castor bean dust was common among castor oil factory workers, presenting as an increased incidence of asthma. 9

A review of anaphylactic reactions to IV phytonadione suggested that the vehicle polyoxylated castor oil was responsible. No previous exposure or sensitization was documented for the reaction. 16

Toxicology

R. communis is a commonly cultivated plant, and ornamental use of the beans makes them attractive to small children. The leaves and seeds of the plant contain the toxic protein ricin and the alkaloid ricinine. 21 , 22 Nonetheless, deaths from castor plant or bean are rare. Between 1983 and 2002, no deaths were recorded by the American Association of Poison Control Centers, 3 , 4 , 23 and more recent analyses of case reports suggest that toxicity from castor poisoning is usually not severe. 3 , 4

Toxicity of ricin is dependent on both the dose and the route of administration. Intracellular uptake of ricin is relatively slow; however, a small number of molecules can cause cell death via irreversible inactivation of ribosomes leading to inhibition of protein synthesis. 3 , 4 , 5 In a primate study, a dose-dependent latency to onset of symptoms of up to 24 hours was demonstrated following inhalation exposure, with death occurring within 36 to 48 hours. 4

The mean lethal dose is lowest for the inhalational route and highest for the intragastric route. Inhalation of castor bean dust may lead to pulmonary and systemic effects in factory workers. Poor absorption results from ingestion of the bean as enzymatic degradation occurs. Contact dermatitis has been reported, but dermal absorption is poor. 4 Experiments in rats and mice to determine the distribution of ricin found 50% to 68% of the IV dose in the liver, muscle, and spleen. 3 , 4 Parenteral doses of ricin up to 20 mcg/m 2 in clinical trials were well tolerated, with adverse reactions of flu-like symptoms and muscle pain reported. 3 , 4 , 5

Management of castor or ricin poisoning is generally symptomatic. 3 , 23 Administration of IV fluids and electrolytes is the standard response, but gastric lavage is appropriate if the beans or plant parts have been chewed. If the seeds have been swallowed whole, poisoning is unlikely to occur. 3 , 23 Symptoms of poisoning include nausea, vomiting, abdominal cramps, diarrhea, dehydration, GI hemorrhage, anuria, fever, and hypotension, as well as signs of liver and renal toxicity. 3 , 4